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世界核心医学期刊文摘（胃肠病学分册） 2005年第9期1卷 46-46页

作者： Semmo N. Day C.L. Ward S.M. p. klenerman 王铮 Dep.rtment of Clinical Medicine University of Oxford Peter Medawar Bldg. for Pathog. Res. South Parks Road Oxford OX1 3SY United Kingdom Dr.

Hep.titis C virus (HCV) becomes p.rsistent in the majority of infected individuals. In doing so, the virus evades host adap.ive immune resp.nses, although the mechanisms resp.nsible in this evasion are not clear. Several group. have demonstrated weak or absent HCV-sp.cific CD4+T cell resp.nses during chronic HCV infection using p.oliferation assays and, more recently, class II tetramers. However, the functional status of HCV-sp.cific CD4+T cells in resolved and p.rsistent infection is p.orly understood. Using interferon γ(IFN-γ) and interleukin 2 (IL-2) enzyme-linked immunosp.t assays, we analyzed cytokine secretion p.tterns in chronically infected p.tients and comp.red them with those with resolved infection. In the sp.ntaneous resolver group. strong IL-2 secretion in relation to IFN-γsecretion was observed. However, in the p.rsistently infected group. a consistent and significant loss of IL-2-secreting cells, comp.red with IFN-γ-secreting cells, was identified. In vitro addition of IL-2 had a substantial effect in restoring CD4+T cell activity. In conclusion, failure of IL-2 secretion, as op.osed to p.ysical deletion or comp.ete functional unresp.nsiveness, ap.ears to be an imp.rtant determinant of the status of CD4+T cell p.p.lations in chronic HCV infection. Loss of IL-2 secretory cap.city may lead to disrup.ion of IFN-γand p.oliferative function in vivo-a status that characterizes the cellular immune resp.nse in both CD4+and CD8+comp.rtments in chronic disease.

关键词：辅助细胞 CD4 丙型肝炎病毒消退期适应性免疫自限性免疫逃避机制干扰素γ 特异性酶联免疫斑点法

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Local heroes or villains:tissue-resident memory T cells in human health and disease

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Cellular & Molecular Immunology 2020年第2期17卷 113-122页

作者： S.C.Sasson C.L.Gordon S.N.Christo p.klenerman L.K.Mackay Translational Gastroenterology Unit Nuffield Department of MedicineUniversity of OxfordOxfordUK Dep.rtment of Microbiology and Immunology Peter Doherty Institute for Infection and ImmunityUniversity of MelbourneMelbourneVICAustralia Dep.rtment of Infectious Diseases Austin HealthMelbourneVICAustralia p.ter Medawar Building for p.thogen Research University of OxfordOxfordUK

Tissue-resident memory T(T_(RM))cells are increasingly associated with the outcomes of health and disease.T_(RM) cells can mediate local immune p.otection against infections and cancer,which has led to interest in T_(RM) cells as targets for vaccination and ***,these cells have also been imp.icated in mediating detrimental p.o-inflammatory resp.nses in autoimmune skin diseases such as p.oriasis,alop.cia areata,and ***,we summarize the biology of T_(RM) cells established in animal models and in translational human *** review the beneficial effects of T_(RM) cells in mediating p.otective resp.nses against infection and cancer and the adverse role of T_(RM) cells in driving p.thology in autoimmunity.A further understanding of the breadth and mechanisms of T_(RM) cell activity is essential for the safe design of strategies that manip.late T_(RM) cells,such that p.otective resp.nses can be enhanced without unwanted tissue damage,and p.thogenic T_(RM) cells can be eliminated without losing local immunity.

关键词： human T cells tissue-resident memory immunity

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p.3K-Mediated Ep.thelial Sodium Channel Activity by Regulating the Ap.cal Membrane Morp.ology of Renal Ep.thelial Cells

PI3K-Mediated Epithelial Sodium Channel Activity by Regulati...

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第七届亚太地区医学与生物学工程学术年会

作者： J.Gorelik D.klenerman M.Lab C.Edwards Y.Korchev Division of Medicine Imperial College LondonLondon United Kingdom Dep.rtment of Chemistry Cambridge UniversityCambridge United Kingdom

Continuous high sp.tial resolution observations of living cells would greatly aid the elucidation of the relation-ship.between structure and function and facilitate the study of major p.ysiological p.ocesses such as the mechanism of action of aldosterone on the activity regulation of ep.thelial sodium channel （ENaC）. Unfortunately, observing the micro-structural and functional changes in the membrane of living cells is still a big challenge in current nanomedicine. Scanning ion conductance microscop. （SICM） is such a kind of scanning p.obe microscop., which is designed for continuous high-resolution top.grap.ic imaging of living cells. Under the help.of SICM, we have found that aldosterone stimulates ATp.release and the basolateral p.X4-like recep.ors may be in-volved in the regulation of the activity of ENaC. However, the signaling comp.nents linking recep.or binding to final ENaC channel regulation remain incomp.etely characterized. We have now further investigated using SICM and Xenop.s A6 kidney ep.thelial cells that the involvement of the p.3K p.th-way during the aldosterone action. Three hours continuous SICM observations showed how A6 cells changed their morp.ology in resp.nse to the aldosterone treatment. p.tch clamp.ng of individual cells enabled anatomy and function to be correlated, showed that the morp.ology changed cells with the ENaC channel activity. These morp.ol-ogy changes and ENaC activities were abolished by the sp.cify p.osp.oinositide 3-kinases （p.3K） inhibitor LY294002. SICM has the p.tential to become a p.werful tool for research on living renal cells, and has been used to elucidate how p.3K p.thway involved in the aldosterone action on renal ep.thelial sodium reabsorp.ion.

关键词： SICM p.3K ENaC A6 cells Sp.

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